Epidemiology of multiple sclerosis in Qom: Demographic study in Iran.

BACKGROUND
Recent studies have demonstrated controversial results and somewhat increased frequency of multiple sclerosis (MS). We reevaluated the files of MS patients from Qom Province of Iran in order to investigate the epidemiology of the disease.


METHODS
Demographic and clinical records of 592 MS patients were reviewed, which included; age, sex, date of birth, marital and occupation status, presenting symptoms, time of onset, type and family history of MS, and history of autoimmune or other diseases.


RESULTS
At the time of our study, 11 patients had died, and 581 were alive with a total female-to-male ratio of 3.4. The mean age of onset of the disease was 34.25 ± 9.01 for all the patients. 11.2% of patients had positive family history of MS. The majority of patients (80.1%) showed relapsing-remitting (RR) pattern. The prevalence of MS was calculated as 50.4/100000 for Qom.


CONCLUSION
Qom is located within a high risk zone of MS. Although we found evidences about the role of environmental factors, geographical distribution, and etcetera, many more studies need to be performed in this respect.


immune respo
se to myelin antigens may be implicated in the pathogenesis of MS. 3,4 However, the actual cause of the disease remains to be elucidated.

Evidences from studies of different populations over various geographical areas suggested that a complicated interaction of genetic and environmental factors may be involved in the development of MS. 5,6 A theory that could be further su ported by highly informative epidemiologic studies. 7Indeed, it is believed that achieving a good knowledge of the epidemiology of MS gives new insights into the underlying causes of the disease.

Although many studies have shown significant variance in the prevalence of MS within diverse populations and different geographic areas, a unique geographic distribution for MS has been suggested by many investigators.][13][14] Based on t e division of Kurtzke, Iran lies within a low risk zone (less than 5/100000) of MS prevalence. 8,9][17][18][19] In this study, we reevaluated the files of 581 patients from Qom province in order to investigate the epidemiology of MS in this province.


Materials and Methods


Study Area

This study was conducted during February 2011 to August 2011 in Qom Province located in the center of Iran, within the latitudes and the longitudes, 34.15°-35.15°N and 50.30°-51.30°E, respectively.It is 11237 km² in area, coverings 0.8.6% of the total area of the country, and was a part of Tehran province until 1995.Since Qom province is situated beside an arid region, it has a dry, desert, and semi-desert climate with inadequate rainfall and low humidity. 20


Population at Risk

According to the 2011 census, the total population of Qom province was 1151672 people among which 564011 (48.97%) were women and 587661 (51.03%) men, and out of which 1095871 (95.15%) lived in urban areas, 55798 (4.85%) in rural vicinities, and 3 in an undisclosed place. 21


Data Collection

Demographic and clini

ents of Qom
province were obtained from Iranian MS Society (IMSS) and mostly from the MS Society of Qom (MSQ), both non-governmental organizations established in 1999 and 2003, respectively, and reviewed.As some habitants of Qom suffering from MS travel to Tehran for treatment, their documents were accessible through IMSS.In the cases of insufficient information or missing data, if possible, phone contacts with the patients were made; otherwise, they were excluded from the stu

.Note that all the
atients included in this study had been living in Qom for the last 10 years before the onset of the disease.

Since MSQ is the unique NGO in Qom for MS patients, and the membership in MSQ and IMSS facilitates the accessibility of some drugs including interferon beta; the pati

ts voluntarily r
fer to these societies.They are registered by presenting a confirmation letter from the neurologist who has diagnosed the disease based on the worldwideaccepted criteria of Poser et


Results

Among 592 registered patients in MSQ and IMSS, 581 were alive and 11 had died at the time of our investigation; their information was not included in our analysis.Based on the information by the 2011 census that estimated the population of Qom province to be 1151672, and considering the total of 581 MS patients of Qom, the prevalence of the disease was calculated as 50.4/100000 for this province.Unfortunately, as one of the limitations of our study, it was not poss ble to calculate the incidence of MS disease in Qom.Demographic features and some life style factors of the included patients are given in table 1.The percentage of the women with MS exceeds that of the men, showing a total female-to-male ratio of 3.4.Table 2 summarizes the family history of MS, and other autoimmune disorders, and personal childhood history of inf

tious (v
ral) diseases.11.2% of patients had positive family history of MS among their first-degree relatives, and 19.5% of them hold family history of other autoimmune diseases (Table 2).As illustrated in figure 1, the patients born in summer and in August were more frequent than other seasons and months, and a minority of the patients was born in autumn and October.However, no significant differences were shown between them.In our study, the first episode of neurological impairment, lasting for 24 hours stated by the patients, was considered as the onset of MS, regardless of the diagnosis of the disease.The mean age of onset of the disease was calculated to be 34.25 ± 9.01 for all the patients, 33.63 ± 8.83 for women, and 36.41 ± 9.34 for men. Figure 2 categorizes the patients in four age groups ranging from bellow 20 year olds up to 50 year olds.As illustrated in this figure, approximately half of the patients, both women and men, were 21-30 years old when the disease started, while a minority of them was 41-50.We conceder the age bellow 16 years as an early-onset age, and above 50 years as late-onset age of MS. 24 In total, 2.6% of the patients involved in our study appeared to be in the early-onset age and none of the patients were in the late-onset-age category.

With respect to the type of MS, depicted in figure 3, the majority of the patients (80.1%) suffered from relapsing-remitting (RR), both women (83.5%) and men (68.3%), at the time of registration.The patients with secondary-progressive (SP) pattern, also appeared with considerable frequency (14.0%); likely more common among men and with a female-to-male ratio of 0.55.According to table 3, the time interval between the onset of disease and definite MS diagnosis are categorized as less than 6 months (53.1%), from 6 months to 1 year (21.2%), and more than 1 year (25.7%).In addition, with respect to the presenting symptoms of the disease, higher frequencies were calculated for sensory (38.7%), visual (35.9%), and motor (12.7%) signs.

The amount of time of exposure to the sun ranged from 0 to more than 240 minutes per day among the MS patients.49.4% an 35.1% of the women were exposed to the sun for 0-10 and 11-30 minutes daily, respectively.In contrast, 25.4% of men were exposed for 0-10 minutes, and 32.5% for 11-30 minutes to the sun (figure 4).


Discussion

Iran has been previously thought to be located in the low risk zone of MS prevalence. 9,25However, recent epidemiological investigations by Etemadifar et al., and Saadatnia et al. in Isfahan, a province in the center of Iran with a homogeneous racial background, suggested a medium-to-high risk level of MS prevalence in the province. 15,16They reported a prevalence of 35.5/100000 and 43.8/100000, respectively.In addition, recently, our study group in a demographic study of 8000 patients from Tehran, the most populated provin e of the country with a heterogeneous racial background, confirmed the findings of Etemadifar et al., and Saadatnia et al. 15,16,26 This study presented a prevalence of 51.9/100000 in Iran.More recently, Moghtaderi et al., in an epidemiological study of MS in the southeastern part of Iran, concluded that the incidence rate of MS shows a faster growth rate, compared to previous years. 17urthermore, Hashemilar et al. reported that MS prevalence in North West of Iran lies in the medium frequency range. 18Similarly, Jajvandian et al. have described a medium risk area for definite MS in the North East of Iran. 1919,26 Based on our findings, Tehran and Qom have the highest prevalence of MS in comparison with other parts of Iran.Regarding a medium prevalence of MS reported for South East, North West, and North East of Iran; it seems that the distribution of MS does not follow a definite pattern. 17- 198][29][30][31] However, more investigations must be done.

It is believed that MS is predominant among women compared to men. 14,32,33In agreement with previouse studies, and according to the resu ts presented by Kalanie et al. and recently by our group, female preponderance has been observed among Iranian MS patients. 26,33This is now further supported by the results of the peresent study, showing a femaleto-male ratio of 3.4.Moreover, the results of the present study revealed that the RR type was the predominant pattern of MS, either totally or among the women, which is in accordance with previous reports. 26,33However, we found that SP MS was rather more common than primary progressive (PP) MS, at the time of registration.Moreover, the number of men suffering SP and or PP exceed that of women, that is not in accordance with our previos findings, and findings of Montalban and Rio and Kalanie et al. 26,33,34 They have shown a high frequency of PP, compred to SP, and dominant number of women with PP or SP in comparison with men.

The results of the present study estimated that the mean age of the onset of MS in women is less than men, approximately 3 years.Additionally, 70.8% of the patients were 20-40 years old when the first episode of neurological impairments had occurred, and only 2.6% of the patients faced the early onset of MS.It seems that MS mostly occurs in adults, and the late-onset age, calculated 0.0% in the present study, and the early-onset age, both account for an inconsiderable percentage of the onset-age of the disease among the Iranian population.This is in-line with our previous results and with those of many other investigations. 16,26,35,36In addition, regarding gender and type of disease, most of the patients are diagnosed within 6 months after the onset of the disease, which is in agreement with our previous findings. 26e found about a three times higher prevalence of MS among married people, both the women and the men, than single patients.In addition, widowed or divorced patients, compared to single patients, appeared to be at a lower risk level.These results are in agreement with our former data from investigating the epidemiology of MS in Tehran. 26Unfortunately, as the weakness of our study, we could not involve the spouses of the patients in the study, and we also did not know whether the disease happened before the marriage or after.Moreover, there are few studies concerning the role of marriage status in MS. 37 It is suggested that in general, individuals with MS have a genetic predisposition to autoimmunity. 38urthermore, autoimmune disease is more common in first-degree relatives of patients with MS; therefore, common genetic susceptibility factors for autoimmunity co-exist with additional disease specific genetic or environmental factors. 39Our results indicated that the familial rate among MS patients from Qom province is 11.2%, which is closer to the commonly-accepted rate reported by Compston, and in line with the studies of El-Salem et al., and Ebers et al. 31,40,41 In addition, we found that a considerable percentage of the patients hold a family history of other autoimmune diseases.3][44][45][46] We observed that a considerable number of the patients had experienced Chickenpox, Measles, and Mumps during their childhood, which may support the association between viral infections and MS; though, this remains to be well-elucidated.http://ijnl.tums.ac.ir 6 October Seasonal effects on risk of MS has been suggested by many studies, describing the patients born in spring with higher frequency of MS births and those born in the autumn with less frequency of MS. [47][48][49][50] However, exceptions have also been reported. 51,52According to the results of the presen

study, the majority of patients w
re born in summer and in August and the patients born in autumn and in October appeared with less frequency.Our no significant differences among months and seasons of both of the MS patients.This is in agreement with the studies by Givon et al. and Staples et al. 51,52 However, this is in discordance with the study of Bayes et al., who have mentioned the peak season and month to be spring and April, respectively. 48However, the month and season of birth needs further research to be considered as a climaterelated environmental factor involved in susceptibility to MS.It is thought that exposure to sunlight, due to its role in vitamin D production, is involved in the development of MS. [53][54][55][56] Our findings might support the previous data about the role of the reduction in exposure to sunlight in determining the rate of MS. [53][54][55][56]


Conclusion

According the results of the present study, Qom is located within a high risk zone of MS.In addition, regarding the previous studies in other provinces of Iran, the pattern of MS distribution does not seem to follow the latitude theory.Moreover, in Qom, women are probably at a higher risk of the disease, and the season and month of birth, and lack of adequate sunlight exposure may be effective in the risk of the disease.

Figure 1
1
Figure 1.Fre The patients b




Figure 3. Ty The majority of registration


Figure 4
4
Figure 4. Th 49.4% and 35 11-30 minute


Table 1 .
1
Demographic features and some life style factors of MS patients of Qom
CharacteristicsVariations n (%)Frequency n (%)TotalGenderFemale Male449 (77.3) 132 (22.7)581Single124 (22.1)Marital statusMarried40